The objective is to define some of the processes involved in the initiation and maintenance of high blood pressure. We have previously observed in the spontaneously hypertensive rat (SHR) a decreased number of small arterioles in the early hypertensive phase. Our long term goal is to explore the possibility that this decreased number of small arterioles is involved in the hypertensive process and to determine the mechanism(s) whereby this rarefaction of vessels occurs. Utilizing previously developed in vivo photomicrographic methods for determining microvascular anatomy in the cremaster muscle we plan to follow the development of the decrease in number of small arterioles in the SHR. We also plan to confirm these findings in the SHR using injection and histological methods and different tissues and extend these studies to rats with induced hypertension (DOCA, renovascular, etc. Alterations in microvascular patterns in human hypertensives will also be documented using conjunctival photomicrography. Finally, we propose to investigate the mechanism(s) of the reduced number of arterioles by means of pharmacologic blockade and chemical interventions. These studies offer the potential for a better understanding of some of the basic mechanisms involved in the hypertensive process and since a sizeable portion of this project is concerned with mechanism(s) regulating vascularization, the findings are of importance in the areas of collateralization of ischemic tissues, vascularization of tumors and ageing.